Leucine-rich glioma inactivated 3 and tumor necrosis factor-α regulate mutually through NF-κB

•LGI3 and TNF-α upregulated each other in 3T3-L1 preadipocytes.•LGI3 increased TNF-α expression through NF-κB binding to a site (−523 to −514) in TNF-α promoter.•TNF-α increased LGI3 expression through NF-κB binding to a site (−40 to −31) in LGI3 promoter.•LGI3 and TNF-α were increased and colocalized in adipose tissue inflammation in obese mice.•The mutual upregulation of LGI3 and TNF-α may play a role in adipose tissue inflammation in obesity.

Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 increased in obese adipose tissues and suppressed adipogenesis through its receptor, ADAM23. We proposed that LGI3 may be a pro-inflammatory adipokine secreted predominantly by preadipocytes and macrophages. In this study, we showed that LGI3 and tumor necrosis factor-α (TNF-α) upregulated each other in 3T3-L1 cells. Treatment of 3T3-L1 preadipocytes with LGI3 protein increased TNF-α mRNA and protein. LGI3 treatment led to NF-κB activation and binding to an NF-κB binding site (−523 to −514) in TNF-α promoter. TNF-α treatment increased mRNA and protein expression of LGI3 and ADAM23. TNF-α increased NF-κB binding to a predicted binding site (−40 to −31) in LGI3 promoter. High fat diet-fed mice showed that LGI3 and TNF-α were increased and colocalized in adipose tissue inflammation. Taken together, these results suggested that mutual upregulation of LGI3 and TNF-α may play a role in adipose tissue inflammation in obesity.